It has been known for some time that contraception can be achieved by the oral administration of sufficient quantities of a progestogen to a female of child-bearing age.
For example in French Patent Application No. 2,223,018 to Ortho Pharmaceutical, a progestogen is administered from at least the fifth day to the twenty-fifth day of the menstrual cycle, the dosage of the progestogen being greater during the last seven days of administration than it is in the first seven days.
U.S. Pat. No. 4,018,919 to Eli Lilly & Co. describes a sequential oral contraceptive method using two different types of progestational agents. These different types of progestational agents are a Type A progestin (e.g. norethindrone) and Type B progestin (e.g. chlormadione acetate).
Another contraceptive regimen using these two types of progestational agents is described in Belgian Patent 773,064 to Ciba Geigy AG.
U.S. Pat. No. 4,171,358 to Eli Lilly & Co. describes another contraceptive method in which a progestin (e.g. chlormadione acetate) is administered on days 6 to 16 of the menstrual cycle, followed by a period in which no hormone is administered.
DT 1,950,857 to Merck Patent GmbH describes a progestogen-only contraceptive pack containing 28 dosage units, 14 to 18 of which are "blanks", containing no contraceptive steroid. Disclosed progestogens include chlormadione acetate, megestrol acetate, melengestrol acetate and medroxyprogesterone acetate. A similar regimen is disclosed in DT 1,965,881, also to Merck Patent GmbH.
U.S. Pat. No. 3,822,355 to Biological Concepts Inc. describes a method of controlling the ovulatory cycle in women involving administering placebo tablets daily for 12 to 16 days; followed administering daily tablets containing 2 to 20 mg progestogen (e.g. norethindrone) for four days; finally followed by administering tablets containing 10 to 40% of the previous progestogen dosage for the remainder of the cycle.
"Progestogen-only pills" are a preferred method of contraception for breast-feeding mothers, older women, Women for whom estrogen is contraindicated, women who are hypertensive, and women who develop migraine headaches when taking a combined pill (i.e. one containing an estrogen and progestogen component). See, e.g. "Contraception for women over the age of 35", IPPF Medical Bulletin, 22: 3-4 (1988) and Howie, PW "The progestogen-only pill" Brit. J. Obstet. Gynaecol., 92: 1001-2 (1985).
While different progestogen-only regimens have been described, they are still associated with incomplete ovulation inhibition, and relatively high failure rates. Vessey et al "Progestogen-only oral contraception. Findings in a large prospective study with special reference to effectiveness", Brit. J. Family Planning, 292: 526-30 (1986). It has been suggested to increase the daily dosage of progestogen in order to induce complete ovulation inhibition, however such an increase in dosage also increases the frequency of intermenstrual bleeding (i.e. "spotting"), which is clearly not desired. E. Diczfalusy et al, Progestogens in Therapy, p. 150 (Raven Press, N.Y. 1983).
Moreover, a high prevalence of functional ovarian cysts have been reported with progestogen only contraceptive regimens, which resolve after discontinuation of the progestogen-only contraceptive. Fotherby, K. "The Progestogen-pill" in: Filshie et al eds. Contraception: Science and Practice, pp. 94-108 (1989), and Howie, supra.
A need exists for a progestogen-only contraceptive regimen which more effectively inhibits ovulation, while still not increasing the frequency of intermenstrual bleeding, or leading to persistent functional ovarian cysts.